US20110135058A1 - Method and system for administering internal radionuclide therapy (irt) and external radiation therapy (xrt) - Google Patents

Method and system for administering internal radionuclide therapy (irt) and external radiation therapy (xrt) Download PDF

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US20110135058A1
US20110135058A1 US12/687,670 US68767010A US2011135058A1 US 20110135058 A1 US20110135058 A1 US 20110135058A1 US 68767010 A US68767010 A US 68767010A US 2011135058 A1 US2011135058 A1 US 2011135058A1
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dose
image information
irt
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George Sgouros
Robert Hobbs
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Johns Hopkins University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103Treatment planning systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103Treatment planning systems
    • A61N5/1031Treatment planning systems using a specific method of dose optimization
    • A61N2005/1034Monte Carlo type methods; particle tracking
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103Treatment planning systems
    • A61N5/1038Treatment planning systems taking into account previously administered plans applied to the same patient, i.e. adaptive radiotherapy

Definitions

  • FIG. 1A illustrates a system for administering internal radionuclide therapy (IRT) and/or external radiation therapy (XRT), according to one embodiment.
  • IRT internal radionuclide therapy
  • XRT external radiation therapy
  • FIG. 1B illustrates a computerized method for determining an optimum amount of radioactivity to administer to a patient, according to one embodiment.
  • FIG. 2 illustrates how the absorbed dose rate information can be integrated over time for a VOI in an example patient, according to one embodiment.
  • FIG. 3 sets forth details of how IRT total dose image information can be used to obtain total dose image information that is radiobiologically equivalent to XRT total dose image information, according to one embodiment.
  • FIGS. 4-6 illustrate example cumulated dose volume histograms.
  • FIG. 7 illustrates an example combined therapy plan.
  • FIG. 8 illustrates an example of how images from different time points can be registered to each other across time.
  • FIG. 1A illustrates a system 100 for administering internal radionuclide therapy (IRT) and/or external radiation therapy (ERT), according to one embodiment.
  • at least one detector e.g., camera 155
  • images an imaged object 160 e.g., a person, a phantom
  • a camera 155 e.g., positron emission tomography (PET) camera, gamma camera
  • PET positron emission tomography
  • gamma camera can be a device used to image gamma radiation emitting radioisotopes. It can be used to view and analyze images of the human body or the distribution of radionuclides emitting gamma rays (e.g., to treat cancer).
  • the camera 155 can be connected to a computer application 150 that can control the operation of the camera and/or the acquisition and storage of acquired images.
  • the computer application 150 can accumulate events, or counts, of gamma photo
  • Effective cancer treatment can require combination therapies.
  • the combination of external radiation (beam) therapy (XRT) with internal radionuclide therapy (IRT) requires accurate three dimensional dose calculations to avoid toxicity and evaluate efficacy.
  • a treatment planning methodology can be performed using a patient-specific three-dimensional radiobiologic dosimetry package (3D-RD) for sequentially combined IRT/XRT therapy using computer application 110 .
  • 3D-RD patient-specific three-dimensional radiobiologic dosimetry package
  • this therapy can limit toxicity to organs at risk.
  • a voxelized IRT absorbed dose (AD IRT ) value obtained using the software package 3D-RD, can be directly converted into an equivalent two-Gray-fraction XRT absorbed dose (AD IRT 2GF ), using the BED model.
  • AD IRT 2GF an equivalent two-Gray-fraction XRT absorbed dose
  • FIG. 1B illustrates a computerized method for determining an optimum amount of radioactivity to administer to a patient, according to one embodiment.
  • a method can be provided that incorporates radiobiological modeling to account for the spatial distribution of absorbed dose and also the effect of dose-rate on biological response.
  • the methodology can be incorporated into a software package which is referred to herein as 3D-RD (3D-Radiobiological Dosimetry).
  • 3D-RD 3D-Radiobiological Dosimetry
  • Patient-specific, 3D-image based internal dosimetry can be a dosimetry methodology in which the patient's own anatomy and spatial distribution of radioactivity over time are factored into an absorbed dose calculation that provides as output the spatial distribution of absorbed dose.
  • At least one image can be obtained relating to anatomy of a particular patient.
  • the images can be, for example, one or more computed tomography (CT) images, one or more single photon emission computed tomography (SPECT) images, and/or one or more positron emission tomography (PET) images can be input.
  • CT computed tomography
  • SPECT single photon emission computed tomography
  • PET positron emission tomography
  • multiple images can be obtained regarding radioactivity distribution over time in the particular patient.
  • SPECT/CT images from two different time points (4 h, 48 h) can be input.
  • the SPECT images can be constructed using a quantitative SPECT (QSPECT) method, using, for example, 30 iterations and 16 subsets per iteration, and based on the iterative ordered-subsets expectation-maximization (OS-EM) algorithm with reconstruction-based compensation for attenuation, scatter, and the collimator-detector response function (CDRF).
  • QSPECT quantitative SPECT
  • OS-EM iterative ordered-subsets expectation-maximization
  • CDRF collimator-detector response function
  • the attenuation can be modeled using measured CT-based attenuation maps.
  • Scatter compensation can be performed using a fast implementation of the effective source scatter estimation (ESSE) method.
  • Point sources at various distances from the face of the collimator can be simulated to estimate the distance-dependent CDRF that can include interactions and penetration of photons in the collimator and detector.
  • More information on the QSPECT method can be found in B. He et al., “A Monte Carlo and Physical Phantom Evaluation of Quantitative In-111 SPECT”, Phys, Med. Biol., Sep. 7, 2005, 50(17); 4169-4185, which is herein incorporated by reference.
  • More information on the OS-EM algorithm can be found in H M Hudson et al. “Accelerated Image—Reconstruction Using Ordered Subsets of Projection Data”, IEEE T Med.
  • the multiple images related to the radioactivity distribution can be registered over time.
  • the SPECT/CT images from the two different time points above (4 h, 48 h) can be registered to each other across time by registering the CT portion of the SPECT/CT images on a HERMES workstation.
  • Image registration can result in a set of images that are aligned to each other such that the coordinates of a particular voxel in one image can also be used in the other registered image to identify the same anatomical position (i.e., voxel). This is illustrated in FIG. 8 .
  • radioactivity image information can be combined with anatomy image information for each image to help guide a contour drawing for target and sensitive tissue VOIs.
  • a CT image that is co-registered with a radioactivity distribution image can be loaded into XRT treatment planning software (e.g., Philips Pinnacle Radiation Treatment Planning System, Koninklijke Philips Electronics, Eindhoven, Netherlands) and used to define the aforementioned VOIs.
  • XRT treatment planning software e.g., Philips Pinnacle Radiation Treatment Planning System, Koninklijke Philips Electronics, Eindhoven, Netherlands
  • an outline for the tumor VOI can be drawn on the XRT activity image.
  • a sensitive VOI which is outline for the radiation sensitive dose limiting VOI (e.g., the spinal column)
  • An IRT treatment plan can also be designed, based on delivering a dose of 30 Gy to 90% of the tumor voxels, while minimizing the dose to the spinal column.
  • a spill-out correction can occur.
  • the dose estimation can be skewed in sensitive regions due to high measured activity artificially created in the SPECT or PET emission images, due to spill-out, mis-registration, and/or mis-identification of sensitive VOIs.
  • it is assumed that all activity in excess of the background amount in the sensitive VOI is due to spill-out.
  • the activity values in the sensitive areas which are proximal to the tumor VOI can be replaced with background activity values taken from areas of the spinal column VOI not immediately adjacent to regions of high uptake.
  • FIG. 6 shows that because of the close proximity of the target tumor to the sensitive tissue, in this case the spinal cord, the artifactual maximum absorbed dose (e.g., the maximum absorbed dose due to failure to correct for spill-out) to the spinal cord is 45.7 Gy, whereas, if the spill-out correction is implemented (in FIG. 4 ) and the artifactual activity is replaced with surrounding background activity the true maximum dose to the spinal cord is 6.8 Gy.
  • the artifactual maximum absorbed dose e.g., the maximum absorbed dose due to failure to correct for spill-out
  • a Monte Carlo simulation can be run for each activity image to obtain absorbed dose rate image information at multiple times.
  • a Monte Carlo calculation e.g., using Electron Gamma shower (EGS) Monte Carlo (MC) software
  • EGS Electron Gamma shower
  • MC Monte Carlo
  • Additional information related to the calculation of the Monte Carlo calculations can be found at the following references, which are herein incorporated by reference: Hobbs R et al., “Arterial Wall Dosimetry for Non-Hodgkin's Lymphoma Patients Treated with Radioimmunotherapy”, J. Nucl. Med.
  • the energy deposition distribution from the contributing components from the MC calculation can be weighted for probability and activity.
  • the weighted sum of particulate and photon emissions can be tallied, deposited into each voxel or VOI, and the corresponding energy deposition rate can be divided by the mass of the voxel or VOI as obtained from the product of density and volume, the former by converting the CT houndsfield units into density and the latter by calculating the volume from the voxel dimensions.
  • the final result from the calculation can be the dose-rate for a collection of voxels or for a VOI at a particular point in time, corresponding to the time at which the radioactivity distribution image was collected.
  • the absorbed dose rate image information can be integrated over time, either on a voxelized basis or over a VOI to obtain total absorbed dose image information.
  • FIG. 2 illustrates how the absorbed dose rate information can be integrated over time for a VOI in the example of the 21 year old man.
  • a functional fit can be made for the VOIs as a whole, as well as the individual voxels.
  • the line 215 can represent a monoexponential fit which can be considered, and the effective decay constant can be calculated for each fit.
  • the fit can comprise a linear fit (line 220 ) between the origin (0) and the first time point (4 h), followed by the monoexponential decay (line 215 ). If the decay constant was smaller than the physical decay constant, a second trapezoid can be drawn between the two time points and an exponential tail (line 225 ) with a physical decay constant can be implemented after the second time point (48 h).
  • the resulting area under the curve (under lines 220 , 215 , 225 ) can be calculated as the total absorbed dose image information for IRT, which is (AD IRT ), because FIG. 2 represents the total absorbed dose image information for 153 Sm, which is a type of IRT.
  • the calculation can be performed both on a voxel level, thereby accounting for density and kinetic differences amongst voxels, and also on a whole VOI level wherein the density variations are lost in the sum of total mass assigned to the VOI.
  • the AD IRT information can be used to obtain IRT total dose image information that is radiobiologically equivalent to XRT total dose image information.
  • the radiobiologically equivalent AD IRT is designated 2GFAD IRT , for absorbed dose delivery in 2 Gy fractions, typical of the dose-rate in which external radiotherapy is delivered.
  • Alternative fraction schemes can be envisioned, for example larger (e.g., 3 Gy) or smaller dose fractions could be handled in the manner described herein.
  • FIG. 3 sets forth details of how IRT total dose image information can be used to obtain total dose image information that is radiobiologically equivalent to XRT total dose image information ( 140 ).
  • the AD IRT image information can be converted to equivalent AD IRT 2GF image information. This can be accomplished without the need to generate BED image information using Eq. 5.
  • ⁇ and ⁇ are the radiobiological parameters from a linear quadratic equation
  • D IRT is the IRT absorbed dose
  • AD IRT is the IRT absorbed dose
  • G(T) is the Lea-Catcheside G-factor. Additional information on the linear quadratic equation can be found in J F Fowler, “The Linear-Quadratic Formula and Progress in Fractionated Radiotherapy”, BR. J. RADIOL., August, 1989, VOL. 62 (740): 679-694. Additional information on the Lea Catcheside G-Factor can be found in W T Miller, “Application of the Linear-Quadratic. Model with Incomplete Repair to Radionuclide Directed Therapy”, BR. J. RADIOL., March 1991, VOL.
  • the G-factor can be a function of another radiobiological parameter, ⁇ , which can be the DNA repair rate.
  • another radiobiological parameter
  • the generalized expression of the G-factor is:
  • G ⁇ ( T ) 2 D IRT 2 ⁇ ⁇ 0 T ⁇ D .
  • IRT ⁇ ( t ) ⁇ ⁇ ⁇ t ⁇ ⁇ 0 t ⁇ D .
  • IRT ⁇ ( w ) ⁇ ⁇ ⁇ - ⁇ ⁇ ( t - w ) ⁇ ⁇ w ( Equation ⁇ ⁇ 2 )
  • T represents the radiation exposure duration
  • t and w are integration variables, both representing time.
  • the G-factor can reduce to the formula:
  • represents the dose-rate constant
  • u represents the repair rate constant
  • the BED can be obtained by numerical integration of the general form of G(T). This is described in Hobbs RF et al., “Calculation of the Biological Effective Dose for Piecewise Defined Dose-Rate Fits”, Med. Phys., (March 2009), Vol. 36 (3): 904-907, which is herein incorporated by reference.
  • D XRT can be the XRT absorbed dose
  • Equation (1) a conversion formula for D IRT such that the dose is expressed so that it is radiobiologically equivalent to XRT in terms of dose-rate.
  • D IRT dGF the notation D IRT can be replaced by D IRT dGF , i.e., the absorbed dose from IRT in values consistent with XRT delivered in d Gray fractions:
  • D IRT dGF D IRT ⁇ ( ⁇ / ⁇ + G ⁇ ( ⁇ ) ⁇ D IRT ) ( ⁇ / ⁇ + d ) ( Equation ⁇ ⁇ 5 )
  • Equation (5) can give average voxel 2-Gray-equivalent absorbed doses, AD IRT 2GF , from IRT, calculated using 3D-RD, of 22.6 Gy and 3.9 Gy for the tumor and spinal column, respectively, with a maximum spinal cord voxel dose of 6.8 Gy. Details regarding how this is determined are provided in the following references, which are herein incorporated by reference: Hobbs R et al., “Arterial Wall Dosimetry for Non-Hodgkin's Lymphoma Patients Treated with Radioimmunotherapy”, J Nucl Med.
  • FIGS. 4-6 show cumulated dose volume histograms (DVHs) in FIGS. 4-6 .
  • the percentage of organ volume (shown on the y-axis) within the designated tissue (e.g., spinal cord, tumor) receiving an absorbed dose less than or equal to the Gray value (shown on the x axis) is illustrated.
  • FIG. 4 illustrates a situation where 60% of the tumor volume receives an absorbed dose of 20 gray or less
  • the AD IRT 2GF image information can be used to obtain summed, XRT-equivalent dose image information for any chosen anatomical regions.
  • the AD IRT 2GF image information can be imported into XRT software (e.g., Pinacle) and added to a pre-established external treatment plan multiplied by a factor k, such that the highest total voxel absorbed dose (AD sum 2GF ) in the sensitive region is equal to the maximum tolerated dose (MTD) for that organ.
  • MTD maximum tolerated dose
  • the MTD for the spinal cord can be 50 Gy.
  • the mathematical formulation of this process can be given by:
  • the scale factor k i can be calculated which delivers the MTD, given an AD XRT value from XRT of (D XRT ) i and an AD IRT 2GF value from IRT of (D IRT 2GF ) i .
  • the smallest of all k i values is taken as the scale factor that is actually used, k.
  • the MTD limit may need to be placed on each voxel for serial organs such as the spinal column.
  • a parallel organ can be defined as one in which a sub-set volume exists within the organ that can be killed without substantially impacting the overall functionality of the organ (e.g., a substantial portion of the liver may be killed with minimal threat to the life of a patient).
  • a serial organ can be one in which lethality to any small subvolume of the organ leads to organ failure (e.g., killing of even a small portion of the spinal column can render a patient partially paralyzed).
  • a simple conversion using Equation (3) can be applied to the BED MTD to convert the value to an AD XRT equivalent MTD.
  • AD IRT 2GF component D IRT 2GF
  • D XRT is the calculated external beam AD XRT component that will be administered.
  • XRT could be delivered first, resulting in a given AD XRT and the IRT can be adjusted to deliver the appropriate amount of AD IRT 2GF
  • the voxelized AD IRT 2GF results can be combined with the absorbed doses from the XRT treatment plan (which could be obtained by an intensity modulated radiotherapy treatment (IMRT) procedure), and AD XRT , can be scaled to deliver, for example, a maximum of 50 Gy combined AD sum 2GF to the spinal cord by using Equation (6).
  • IMRT intensity modulated radiotherapy treatment
  • FIGS. 5 and 6 illustrate additional examples.
  • FIG. 5 a illustrates the cumulated dose volume histograms (DVHs) for the baseline IMRT treatment plan
  • FIG. 5 b illustrates the cumulated DVHs for the combined IRT plus scaled IMRT treatment plan.
  • the value calculated for the k-factor for the combined plan was 1.64. Applying this factor to the baseline XRT plan and then summing the two dose-distributions resulted in average voxel AD sum 2GF values of 71.5 Gy and 20.6 Gy for the tumor and spinal column, respectively.
  • FIG. 4 shows the AD sum 2GF isodose contours as well as the VOIs as defined in Pinnacle and used in the 3D-RD calculation.
  • FIG. 6 shows the dose rate kinetics curve from 153 Sm IRT for the tumor VOI considered as a single unit (e.g., the total, rather than individual voxel, dose-rate in the VOI is used for the calculation).
  • the corresponding absorbed dose, AD IRT for the example tumor VOI above is 29.6 Gy.
  • the voxel-averaged absorbed dose, AD IRT is 29.2 Gy, the small difference reflecting the impact of density and kinetic variations within the tumor VOI.
  • the spinal cord is not considered as a single unit since the toxicity is based on the highest dose to a single voxel.
  • the voxel-averaged absorbed dose, AD IRT to the spinal cord is 5.8 Gy.
  • FIG. 7 illustrates an example combined therapy plan.
  • One color e.g., pink
  • PTV planning tumor volume
  • GTV additional gross tumor volume
  • Another color e.g., green
  • GTV additional gross tumor volume
  • Yet another color e.g., yellow

Abstract

A computerized method and system for determining an optimum amount of Internal Radionuclide Therapy (IRT) and External Radiation Therapy (XRT) to administer, comprising: obtaining activity image information for an imaged object from a detector; running a Monte Carlo simulation for the activity image information to obtain absorbed dose-rate image information at multiple times; adding the absorbed dose-rate image information from each time to obtain IRT total absorbed dose image information; and utilizing the IRT total dose image information to obtain total dose image information that is equivalent to XRT dose image information in terms of dose-rate, wherein the IRT dose information is converted to equivalent XRT dose information without having to generate BED dose maps.

Description

  • This application is based on and derives the benefit of the filing date of U.S. Provisional Patent Application No. 61/285,047, filed Dec. 9, 2009, which is herein incorporated by reference in its entirety.
  • This application incorporates by reference U.S. patent application Ser. No. 12/514,853 (filed Sep. 15, 2009) and U.S. Provisional Application 60/860,315 (filed Nov. 21, 2006) and U.S. Provisional Application 60/860,319 (filed Nov. 21, 2006).
  • This invention was made with government support under NIH/NCI grant ROI CA 116477 and DOE grant DE-FG02-05ER63967. The U.S. government may have certain rights in this invention.
  • BRIEF DESCRIPTION OF FIGURES
  • FIG. 1A illustrates a system for administering internal radionuclide therapy (IRT) and/or external radiation therapy (XRT), according to one embodiment.
  • FIG. 1B illustrates a computerized method for determining an optimum amount of radioactivity to administer to a patient, according to one embodiment.
  • FIG. 2 illustrates how the absorbed dose rate information can be integrated over time for a VOI in an example patient, according to one embodiment.
  • FIG. 3 sets forth details of how IRT total dose image information can be used to obtain total dose image information that is radiobiologically equivalent to XRT total dose image information, according to one embodiment.
  • FIGS. 4-6 illustrate example cumulated dose volume histograms.
  • FIG. 7 illustrates an example combined therapy plan.
  • FIG. 8 illustrates an example of how images from different time points can be registered to each other across time.
  • DETAILED DESCRIPTION OF EMBODIMENTS System for Administering IRT and XRT
  • FIG. 1A illustrates a system 100 for administering internal radionuclide therapy (IRT) and/or external radiation therapy (ERT), according to one embodiment. In system 100, at least one detector (e.g., camera 155) images an imaged object 160 (e.g., a person, a phantom) and uses a computer application 110 to process information from the images. A camera 155 (e.g., positron emission tomography (PET) camera, gamma camera) can be a device used to image gamma radiation emitting radioisotopes. It can be used to view and analyze images of the human body or the distribution of radionuclides emitting gamma rays (e.g., to treat cancer). The camera 155 can be connected to a computer application 150 that can control the operation of the camera and/or the acquisition and storage of acquired images. The computer application 150 can accumulate events, or counts, of gamma photons that are absorbed by the crystal in the camera.
  • Effective cancer treatment can require combination therapies. The combination of external radiation (beam) therapy (XRT) with internal radionuclide therapy (IRT) requires accurate three dimensional dose calculations to avoid toxicity and evaluate efficacy. A treatment planning methodology can be performed using a patient-specific three-dimensional radiobiologic dosimetry package (3D-RD) for sequentially combined IRT/XRT therapy using computer application 110. (More information on the 3D-RD package can be found in U.S. patent application Ser. No. 12/514,853, which is herein incorporated by reference.) In one embodiment, this therapy can limit toxicity to organs at risk.
  • In one embodiment, a voxelized IRT absorbed dose (ADIRT) value, obtained using the software package 3D-RD, can be directly converted into an equivalent two-Gray-fraction XRT absorbed dose (ADIRT 2GF), using the BED model. ADIRT 2GF.
  • Method for Administering IRT and XRT
  • FIG. 1B illustrates a computerized method for determining an optimum amount of radioactivity to administer to a patient, according to one embodiment. In one embodiment, a method can be provided that incorporates radiobiological modeling to account for the spatial distribution of absorbed dose and also the effect of dose-rate on biological response. The methodology can be incorporated into a software package which is referred to herein as 3D-RD (3D-Radiobiological Dosimetry). Patient-specific, 3D-image based internal dosimetry can be a dosimetry methodology in which the patient's own anatomy and spatial distribution of radioactivity over time are factored into an absorbed dose calculation that provides as output the spatial distribution of absorbed dose.
  • Referring to FIG. 1B, in 105, at least one image can be obtained relating to anatomy of a particular patient. (Note that a patient is described throughout this document. However, those of ordinary skill in the art will see that a phantom can be used in place of a patient.) The images can be, for example, one or more computed tomography (CT) images, one or more single photon emission computed tomography (SPECT) images, and/or one or more positron emission tomography (PET) images can be input. For example, suppose the patient is a 21 year old man with a four year history of osteogenic sarcoma (a type of bone cancer). SPECT/CT images can be input illustrating the original distribution of the cancer in the 21 year old man.
  • In 110, multiple images can be obtained regarding radioactivity distribution over time in the particular patient. For example, for the 21 year old man, after administration of 16.7 GBq of 153Sm, SPECT/CT images from two different time points (4 h, 48 h) can be input. The SPECT images can be constructed using a quantitative SPECT (QSPECT) method, using, for example, 30 iterations and 16 subsets per iteration, and based on the iterative ordered-subsets expectation-maximization (OS-EM) algorithm with reconstruction-based compensation for attenuation, scatter, and the collimator-detector response function (CDRF). The attenuation can be modeled using measured CT-based attenuation maps. Scatter compensation can be performed using a fast implementation of the effective source scatter estimation (ESSE) method. Point sources at various distances from the face of the collimator can be simulated to estimate the distance-dependent CDRF that can include interactions and penetration of photons in the collimator and detector. More information on the QSPECT method can be found in B. He et al., “A Monte Carlo and Physical Phantom Evaluation of Quantitative In-111 SPECT”, Phys, Med. Biol., Sep. 7, 2005, 50(17); 4169-4185, which is herein incorporated by reference. More information on the OS-EM algorithm can be found in H M Hudson et al. “Accelerated Image—Reconstruction Using Ordered Subsets of Projection Data”, IEEE T Med. Imaging, December 1994, 13(4):601-609, which is herein incorporated by reference. More information on the ESSE method can be found in D J Kadrmas et al., “Fast Implementations of Reconstruction-Based Scatter Compensation in Fully 3D SPECT Image Reconstruction”, Phys. Med. Biol., April 1998, 43(4): 857-873.
  • Referring again to FIG. 1B, in 115, the multiple images related to the radioactivity distribution can be registered over time. For example, the SPECT/CT images from the two different time points above (4 h, 48 h) can be registered to each other across time by registering the CT portion of the SPECT/CT images on a HERMES workstation. Image registration can result in a set of images that are aligned to each other such that the coordinates of a particular voxel in one image can also be used in the other registered image to identify the same anatomical position (i.e., voxel). This is illustrated in FIG. 8.
  • In 120, radioactivity image information can be combined with anatomy image information for each image to help guide a contour drawing for target and sensitive tissue VOIs. For example, a CT image that is co-registered with a radioactivity distribution image (from above) can be loaded into XRT treatment planning software (e.g., Philips Pinnacle Radiation Treatment Planning System, Koninklijke Philips Electronics, Eindhoven, Netherlands) and used to define the aforementioned VOIs.
  • For example, an outline for the tumor VOI can be drawn on the XRT activity image. In addition, a sensitive VOI, which is outline for the radiation sensitive dose limiting VOI (e.g., the spinal column), can be drawn on the XRT activity image. An IRT treatment plan can also be designed, based on delivering a dose of 30 Gy to 90% of the tumor voxels, while minimizing the dose to the spinal column.
  • In 129, a spill-out correction can occur. In some cases, when target VOIs and sensitive VOIs exist in close proximity to each other, the dose estimation can be skewed in sensitive regions due to high measured activity artificially created in the SPECT or PET emission images, due to spill-out, mis-registration, and/or mis-identification of sensitive VOIs. Thus, in some embodiments, it is assumed that all activity in excess of the background amount in the sensitive VOI is due to spill-out. Thus, the activity values in the sensitive areas which are proximal to the tumor VOI can be replaced with background activity values taken from areas of the spinal column VOI not immediately adjacent to regions of high uptake. The impact of such spill-out corrections can be illustrated, for example, in FIGS. 4 and 6. FIG. 6 shows that because of the close proximity of the target tumor to the sensitive tissue, in this case the spinal cord, the artifactual maximum absorbed dose (e.g., the maximum absorbed dose due to failure to correct for spill-out) to the spinal cord is 45.7 Gy, whereas, if the spill-out correction is implemented (in FIG. 4) and the artifactual activity is replaced with surrounding background activity the true maximum dose to the spinal cord is 6.8 Gy.
  • In 130, a Monte Carlo simulation can be run for each activity image to obtain absorbed dose rate image information at multiple times. A Monte Carlo calculation (e.g., using Electron Gamma Shower (EGS) Monte Carlo (MC) software) can be performed to estimate the absorbed dose at each of the activity image collection times by tallying energy deposition in each voxel. Additional information related to the calculation of the Monte Carlo calculations can be found at the following references, which are herein incorporated by reference: Hobbs R et al., “Arterial Wall Dosimetry for Non-Hodgkin's Lymphoma Patients Treated with Radioimmunotherapy”, J. Nucl. Med. (in press)p; Hobbs RF et al., “124I PET-based 3D-RD Dosimetry for a Pediatric Thyroid Cancer Patient: Real-Time Treatment Planning and Methodologic Comparison”, J Nucl Med. (November 2009)m Vol. 50 (11): 1844-7 (Epub 2009 Oct. 16. PubMed PMID: 19837771); Prideaux A R et al., “Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry”, J Nucl Med. (June 2007), Vol. 48 (6): 1008-16 (Epub 2007 May 15. PubMed PMID: 17504874).
  • Thus, for example, using the example above of the 21 year old man, ten million events can be run for the βand photon components of the 153Sm decay spectra based on the SPECT/CT images for the two different time points (4 h, 48 h). The energy deposition distribution from the contributing components from the MC calculation can be weighted for probability and activity. The weighted sum of particulate and photon emissions can be tallied, deposited into each voxel or VOI, and the corresponding energy deposition rate can be divided by the mass of the voxel or VOI as obtained from the product of density and volume, the former by converting the CT houndsfield units into density and the latter by calculating the volume from the voxel dimensions. The final result from the calculation can be the dose-rate for a collection of voxels or for a VOI at a particular point in time, corresponding to the time at which the radioactivity distribution image was collected.
  • In 135, the absorbed dose rate image information can be integrated over time, either on a voxelized basis or over a VOI to obtain total absorbed dose image information. FIG. 2 illustrates how the absorbed dose rate information can be integrated over time for a VOI in the example of the 21 year old man. Using the absorbed dose rates calculated from the Monte Carlo calculation at the two time points (4 h, 48 h) (see triangles), a functional fit can be made for the VOIs as a whole, as well as the individual voxels. The line 215 can represent a monoexponential fit which can be considered, and the effective decay constant can be calculated for each fit. If the decay constant was larger than the physical decay constant (λ>λφ), the fit can comprise a linear fit (line 220) between the origin (0) and the first time point (4 h), followed by the monoexponential decay (line 215). If the decay constant was smaller than the physical decay constant, a second trapezoid can be drawn between the two time points and an exponential tail (line 225) with a physical decay constant can be implemented after the second time point (48 h). The resulting area under the curve (under lines 220, 215, 225) can be calculated as the total absorbed dose image information for IRT, which is (ADIRT), because FIG. 2 represents the total absorbed dose image information for 153Sm, which is a type of IRT. The calculation can be performed both on a voxel level, thereby accounting for density and kinetic differences amongst voxels, and also on a whole VOI level wherein the density variations are lost in the sum of total mass assigned to the VOI.
  • In 140, the ADIRT information can be used to obtain IRT total dose image information that is radiobiologically equivalent to XRT total dose image information. The radiobiologically equivalent ADIRT is designated 2GFADIRT, for absorbed dose delivery in 2 Gy fractions, typical of the dose-rate in which external radiotherapy is delivered. Alternative fraction schemes can be envisioned, for example larger (e.g., 3 Gy) or smaller dose fractions could be handled in the manner described herein.
  • FIG. 3 sets forth details of how IRT total dose image information can be used to obtain total dose image information that is radiobiologically equivalent to XRT total dose image information (140). Referring to FIG. 3, in 305, the ADIRT image information can be converted to equivalent ADIRT 2GF image information. This can be accomplished without the need to generate BED image information using Eq. 5.
  • For background purposes, the derivation of Eq. 5 is outlined below:
  • BED = D IRT ( 1 + G ( ) α / β · D IRT ) ( Equation 1 )
  • where α and β are the radiobiological parameters from a linear quadratic equation, DIRT is the IRT absorbed dose, ADIRT, and G(T) is the Lea-Catcheside G-factor. Additional information on the linear quadratic equation can be found in J F Fowler, “The Linear-Quadratic Formula and Progress in Fractionated Radiotherapy”, BR. J. RADIOL., August, 1989, VOL. 62 (740): 679-694. Additional information on the Lea Catcheside G-Factor can be found in W T Miller, “Application of the Linear-Quadratic. Model with Incomplete Repair to Radionuclide Directed Therapy”, BR. J. RADIOL., March 1991, VOL. 64 (759): 242-251; and D J Brenner et al., “The Linear-Quadratic Model and Most Other Common Radiobiological Models Result in Similar Predictions of Time-Dose Relationships”, RADIAT. RES., July 1998, VOL. 150 (1): 83-91, which are herein incorporated by reference.
  • It should be noted that the G-factor can be a function of another radiobiological parameter, μ, which can be the DNA repair rate. The generalized expression of the G-factor is:
  • G ( T ) = 2 D IRT 2 · 0 T D . IRT ( t ) t 0 t D . IRT ( w ) · - μ ( t - w ) w ( Equation 2 )
  • where T represents the radiation exposure duration, and t and w are integration variables, both representing time.
  • For a monoexponential fit to the dose rates, the G-factor can reduce to the formula:
  • G ( ) = λ λ + μ ( Equation 3 )
  • where λ represents the dose-rate constant, and u represents the repair rate constant.
  • It should be noted that a period of uptake can be expected for some organs and tumors, resulting in kinetics curves that are not well-modeled by monoexponential decay. On a voxel basis, in some embodiments, the kinetics rarely satisfy a mono- or double exponential relationship. In these cases, the BED can be obtained by numerical integration of the general form of G(T). This is described in Hobbs RF et al., “Calculation of the Biological Effective Dose for Piecewise Defined Dose-Rate Fits”, Med. Phys., (March 2009), Vol. 36 (3): 904-907, which is herein incorporated by reference.
  • The BED formula for XRT is given below:
  • BED = D XRT ( 1 + D XRT / N α / β ) ( Equation 4 )
  • where DXRT can be the XRT absorbed dose, ADXRT, N can be the number of fractions of dose d, with DXRT=Nd.
  • By combining Equations (1) and (4), a conversion formula for DIRT such that the dose is expressed so that it is radiobiologically equivalent to XRT in terms of dose-rate. Once the conversion is made, the notation DIRT can be replaced by DIRT dGF, i.e., the absorbed dose from IRT in values consistent with XRT delivered in d Gray fractions:
  • D IRT dGF = D IRT ( α / β + G ( ) · D IRT ) ( α / β + d ) ( Equation 5 )
  • Referring back to the example of the 21 year old man, to determine the 2GFADIRT, if Equation (5) is utilized, the radiobiological parameters can be α/β=5.4 Gy and μ=1.73 Gy−1 for osteosarcoma, α/β=3.33 Gy (30) and μ=0.46 Gy−1 for the spinal cord.
  • For different treatments, different d values can be used. For example; a value of d=2 Gy for therapy can be used in this example, and thus the notation used can henceforth be ADIRT 2GF, where 2GF stands for “two Gray fractions”.
  • For the example above, applying Equation (5) to the voxelized results above can give average voxel 2-Gray-equivalent absorbed doses, ADIRT 2GF , from IRT, calculated using 3D-RD, of 22.6 Gy and 3.9 Gy for the tumor and spinal column, respectively, with a maximum spinal cord voxel dose of 6.8 Gy. Details regarding how this is determined are provided in the following references, which are herein incorporated by reference: Hobbs R et al., “Arterial Wall Dosimetry for Non-Hodgkin's Lymphoma Patients Treated with Radioimmunotherapy”, J Nucl Med. (in Press.); Hobbs RF et al., “1241 PET-based 3D-RD Dosimetry for a Pediatric Thyroid Cancer Patient: Real-Time Treatment Planning and Methodologic Comparison”, J Nucl Med. (November 2009), Vol. 50 (11): 1844-7 (Epub 2009 Oct. 16. PubMed PMID: 19837771); Prideaux A R et al., “Three-Dimensional Radiobiologic Dosimetry Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry”, J Nucl Med. (June 2007) Vol. 48 (6): 1008-16 (Epub 2007 May 15. PubMed PMID: 17504874).
  • These results are illustrated in the form of cumulated dose volume histograms (DVHs) in FIGS. 4-6. In these figures, the percentage of organ volume (shown on the y-axis) within the designated tissue (e.g., spinal cord, tumor) receiving an absorbed dose less than or equal to the Gray value (shown on the x axis) is illustrated. For example, FIG. 4 illustrates a situation where 60% of the tumor volume receives an absorbed dose of 20 gray or less,
  • Referring back to FIG. 3, in 315, the ADIRT 2GF image information can be used to obtain summed, XRT-equivalent dose image information for any chosen anatomical regions. The ADIRT 2GF image information can be imported into XRT software (e.g., Pinacle) and added to a pre-established external treatment plan multiplied by a factor k, such that the highest total voxel absorbed dose (ADsum 2GF) in the sensitive region is equal to the maximum tolerated dose (MTD) for that organ. For example, in the example of the 21 year old man, the MTD for the spinal cord can be 50 Gy. The mathematical formulation of this process can be given by:
  • { k i = MTD - ( D IRT 2 GF ) i ( D XRT ) i k = min { k i } ( Equation 6 )
  • where for each voxel indexed by i, the scale factor ki can be calculated which delivers the MTD, given an ADXRT value from XRT of (DXRT)i and an ADIRT 2GF value from IRT of (DIRT 2GF)i. The smallest of all ki values is taken as the scale factor that is actually used, k.
  • Note that the MTD limit may need to be placed on each voxel for serial organs such as the spinal column. For parallel organs at risk, a single value k for the entire organ may be substituted. In this context a parallel organ can be defined as one in which a sub-set volume exists within the organ that can be killed without substantially impacting the overall functionality of the organ (e.g., a substantial portion of the liver may be killed with minimal threat to the life of a patient). A serial organ can be one in which lethality to any small subvolume of the organ leads to organ failure (e.g., killing of even a small portion of the spinal column can render a patient partially paralyzed). In addition, if the MTD constraint is placed on a BED value rather than an ADXRT value, a simple conversion (using Equation (3)) can be applied to the BED MTD to convert the value to an ADXRT equivalent MTD.
  • Finally, the total absorbed dose (in the 2-Gray fraction equivalent) for each voxel can be given by:

  • D sum 2GF =D IRT 2GF +D XRT  (Equation 7)
  • where the ADIRT 2GF component (DIRT 2GF) has already been delivered and DXRT is the calculated external beam ADXRT component that will be administered. Alternatively, XRT could be delivered first, resulting in a given ADXRT and the IRT can be adjusted to deliver the appropriate amount of ADIRT 2GF
  • In 320, the voxelized ADIRT 2GF results can be combined with the absorbed doses from the XRT treatment plan (which could be obtained by an intensity modulated radiotherapy treatment (IMRT) procedure), and ADXRT, can be scaled to deliver, for example, a maximum of 50 Gy combined ADsum 2GF to the spinal cord by using Equation (6).
  • FIGS. 5 and 6 illustrate additional examples. FIG. 5 a illustrates the cumulated dose volume histograms (DVHs) for the baseline IMRT treatment plan, while FIG. 5 b illustrates the cumulated DVHs for the combined IRT plus scaled IMRT treatment plan. The value calculated for the k-factor for the combined plan was 1.64. Applying this factor to the baseline XRT plan and then summing the two dose-distributions resulted in average voxel ADsum 2GF values of 71.5 Gy and 20.6 Gy for the tumor and spinal column, respectively. FIG. 4 shows the ADsum 2GF isodose contours as well as the VOIs as defined in Pinnacle and used in the 3D-RD calculation.
  • FIG. 6 shows the dose rate kinetics curve from 153Sm IRT for the tumor VOI considered as a single unit (e.g., the total, rather than individual voxel, dose-rate in the VOI is used for the calculation). For example, the corresponding absorbed dose, ADIRT, for the example tumor VOI above is 29.6 Gy. The voxel-averaged absorbed dose, ADIRT , is 29.2 Gy, the small difference reflecting the impact of density and kinetic variations within the tumor VOI. The spinal cord is not considered as a single unit since the toxicity is based on the highest dose to a single voxel. The voxel-averaged absorbed dose, ADIRT , to the spinal cord is 5.8 Gy.
  • FIG. 7 illustrates an example combined therapy plan. One color (e.g., pink) can illustrate the planning tumor volume (PTV) and the volume used in the 3D-RD calculation. Another color (e.g., blue) can illustrate the additional gross tumor volume (GTV). Another color (e.g., green) can illustrate the contour identifying the spinal cord as the sensitive volume. Yet another color (e.g., yellow) can illustrate an artificial VOI used to confine the ADXRT to the GTV, which can be called a “ring”.
  • While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example, and not limitation. It will be apparent to persons skilled in the relevant art(s) that various changes in form and detail can be made therein without departing from the spirit and scope of the present invention. Thus, the present invention should not be limited by any of the above-described exemplary embodiments.
  • In addition, it should be understood that the figures described above, which highlight the functionality and advantages of the present invention, are presented for example purposes only. The architecture of the present invention is sufficiently flexible and configurable, such that it may be utilized in ways other than that shown in the figures.
  • Further, the purpose of the Abstract of the Disclosure is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The Abstract of the Disclosure is not intended to be limiting as to the scope of the present invention in any way.
  • Finally, it is the applicant's intent that only claims that include the express language “means for” or “step for” be interpreted under 35 U.S.C. 112, paragraph 6. Claims that do not expressly include the phrase “means for” or “step for” are not to be interpreted under 35 U.S.C. 112, paragraph 6.

Claims (14)

1. A computerized method for determining an optimum amount of Internal Radionuclide Therapy (IRT) and External Radiation Therapy (XRT) to administer, comprising:
obtaining activity image information for at least one imaged object from at least one detector;
running a Monte Carlo simulation for the activity image information, using at least one computer application, to obtain absorbed dose-rate image information at multiple times;
adding the absorbed dose-rate image information from each time, using at least one computer application, to obtain IRT total absorbed dose image information; and
utilizing the IRT total dose image information, using the at least one computer application, to obtain total dose image information that is equivalent to XRT dose image information in terms of dose-rate, wherein the IRT dose information is converted to equivalent XRT dose information without having to generate BED dose maps.
2. The method of claim 1, wherein the obtaining of the activity image information further comprises:
obtaining at least one image relating to anatomy of at least one imaged object;
obtaining multiple images regarding radioactivity distribution over time;
registering the images related to the radioactivity distribution over time;
combining each radioactivity image with each anatomy image to create activity image information;
3. The method of claim 1, further comprising:
adjusting, using the at least one computer application, at least one IRT dose distribution and/or at least one XRT dose distribution.
4. The method of claim 1, further comprising:
adjusting activity distribution of the at least one IRT dose and/or the at least one XRT dose.
5. The method of claim 3, wherein the adjusting accounts for any already delivered doses.
6. The method of claim 1, wherein the at least one detector is at least one camera.
7. The method of claim 2, wherein the at least one imaged object is at least one phantom and/or at least one person.
8. A computerized system for determining an optimum amount of Internal Radionuclide Therapy (IRT) and External Radiation Therapy (XRT) to administer to a patient, comprising:
at least one detector for obtaining activity image information from at least one imaged object; and
at least one application connected to at least one computer, the at least one application configured for:
running a Monte Carlo simulation for the activity image information to obtain absorbed dose-rate image information at multiple times;
adding the absorbed dose-rate image information from each time to obtain IRT total absorbed dose image information; and
utilizing the IRT total dose image information to obtain total dose image information that is equivalent to XRT dose image information in terms of dose-rate, wherein the IRT dose information is converted to equivalent XRT dose information without having to generate BED dose maps.
9. The system of claim 8, wherein the obtaining of the activity image information further comprises:
obtaining at least one image relating to anatomy of at least one imaged object;
obtaining multiple images regarding radioactivity distribution over time;
registering the images related to the radioactivity distribution over time;
combining each radioactivity image with each anatomy image to create activity image information;
10. The system of claim 8, wherein the at least one computer application is further configured for:
adjusting at least one IRT dose distribution and/or at least one XRT dose distribution.
11. The system of claim 8, wherein the at least one computer application is further configured for:
adjusting activity distribution of the at least one IRT dose and/or the at least one XRT dose.
12. The system of claim 10, wherein the adjusting accounts for any already delivered doses.
13. The system of claim 8, wherein the at least one detector is at least one camera.
14. The system of claim 9, wherein the at least one imaged object is at least one phantom and/or at least one person.
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